Laughter, crying and sadness in ALS

Abstract

Background: Pseudobulbar affect (PBA) is prevalent in amyotrophic lateral sclerosis (ALS), but there is limited information on its associations and course.

Objectives: Explore prevalence, associations, course and manifestations of PBA in outpatient cohort of patients with ALS and examine its relationship to depression.

Methods: Self-reported measures of PBA and depression (Center for Neurologic Study-Lability Scale (CNS-LS) and Patient Health Questionnaire (PHQ-9), respectively) were obtained from consecutive patients with ALS using tablet devices in waiting rooms (Knowledge Program).

Results: PBA (CNS-LS ≥13) was seen in 209/735 patients (28.4%). PBA was associated with bulbar onset and dysfunction, upper motor neuron dysfunction, cognitive impairment, depression and lower quality of life. A multivariable model that included lower bulbar and gross motor subscores, female gender, younger age and shorter duration of disease predicted PBA with 74% accuracy. CNS-LS scores increased only slowly with time. Women with PBA reported more crying than men. Crying (but not laughter) correlated with depression, and crying was associated with poorer quality of life. Exploratory factor analysis of pooled questions of CNS-LS and PHQ-9 identified three underlying factors (laughter, crying and depression) loaded on appropriate questions of the respective instruments.

Conclusion: This study identifies associations of PBA and additionally finds PBA (especially crying-predominant PBA) more prevalent in women with ALS. Although the two self-report instruments (CNS-LS and PHQ-9) discriminate well between PBA and depression, there is significant overlap between depression and crying in PBA. Studies of PBA should stratify for gender, examine crying and laughter as separate outcomes and adjust for depression.

Keywords: CNS-LS; PHQ-9; amyotrophic lateral sclerosis; depression; pseudobulbar affect.

Figure 1

Histograms of Center for Neurologic Study-Lability Scale total score (panel top left), crying and laughter subscores (panel bottom left) and individual questions (panel right).

Figure 2

Optimal multivariable predictive model of pseudobulbar affect (PBA) (Center for Neurologic Study-Lability Scale ≥13) includes five variables. Log odds of PBA are on the y-axis for different values of individual predictors, while other predictors are set at their means or most frequent values. Corresponding function of the linear predictor is displayed in online supplementary table S1. Note that bulbar subscore has a non-linear effect on log odds of PBA (modelled using a restricted cubic spline function), while other variables have a linear effect. The C statistic of predictive accuracy (area under the ROC curve) of this model derived from bootstrap internal validation is 0.74. BulbarSS, bulbar subscore; GrossMotorSS, gross motor subscore. ROC, receiver operating characteristic.